ArticleMolecular cancer therapeutics2022
Olaparib-Induced Senescence Is Bypassed through G2-M Checkpoint Override in Olaparib-Resistant Prostate Cancer.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting NDUFS4 Disrupts Oxidative Phosphorylation and Induces Ferroptosis in Olaparib-Resistant Prostate Cancer.Molecular cancer therapeutics · 2026Article
- Molecular Characterization of PARP Inhibitor Response Reveals Co-Targeting Strategies in Advanced Prostate Cancer.Cancers · 2026Article
- PARP inhibitors induce a senescence phenotype in non-small cell lung carcinoma cell lines.FEBS open bio · 2026Article
- IGFBP3-SphK1/S1P Signaling Axis Drives Enzalutamide Resistance in Advanced Prostate Cancer.Molecular cancer therapeutics · 2026Article
- Liquid Biopsy in Advanced Prostate Cancer.Cancers · 2026Review
- Characterizing Response to PARP Inhibitor Treatment Combinations in Advanced Prostate Cancer.Biomedicines · 2026Article
- The PARP inhibitor olaparib promotes senescence in murine macrophages.GeroScience · 2026Article
- Combination therapy overcomes secondary PARPi resistance in ATM-deficient prostate cancer.NPJ precision oncology · 2025Article
- Kaempferol triggers cellular senescence via CDK1 ubiquitination in HCC cells.Cancer cell international · 2025Article
- Integrative analysis of molecular mechanisms in prostate cancer via single-cell RNA sequencing and weighted gene co-expression network analysis.Scientific reports · 2025Article
- PARP inhibitors elicit a cellular senescence mediated inflammatory response in homologous recombination proficient cancer cells.Scientific reports · 2025Article
- Transcriptomic analysis of Paraoxonase 1 expression in hepatocellular carcinoma and its potential impact on tumor immunity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells.Cancer research communications · 2024Article
- Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients.Journal of experimental & clinical cancer research : CR · 2024Review
- IGFBP3 promotes resistance to Olaparib via modulating EGFR signaling in advanced prostate cancer.iScience · 2024Article
- Triggering pyroptosis enhances the antitumor efficacy of PARP inhibitors in prostate cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Article
- Targeting senescence as an anticancer therapy.Molecular oncology · 2022Review
- PPAR-γ agonist Inactivate Cellular Senescence by Inhibiting SIRT1 Signaling to Confer Increased Sensitivity to Olaparib in Ovarian Cancer Cells.Saudi journal of medicine & medical sciencesArticle
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
PARP inhibition represents the dawn of precision medicine for treating prostate cancer. Despite this advance, questions remain regarding the use of PARP inhibitors (PARPi) for the treatment of this disease, including (i) how specifically do PARPi-sensitive tumor cells respond to treatment, and (ii) how does PARPi resistance develop? To address these questions, we characterized response to olaparib in sensitive LNCaP and C4-2B cells and developed two olaparib-resistant derivative cell line models from each, termed LN-OlapR and 2B-OlapR, respectively. OlapR cells possess distinct morphology from parental cells and display robust resistance to olaparib and other clinically relevant PARPis, including rucaparib, niraparib, and talazoparib. In LNCaP and C4-2B cells, we found that olaparib induces massive DNA damage, leading to activation of the G2-M checkpoint, activation of p53, and cell-cycle arrest. Furthermore, our data suggest that G2-M checkpoint activation leads to both cell death and senescence associated with p21 activity. In contrast, both LN-OlapR and 2B-OlapR cells do not arrest at G2-M and display a markedly blunted response to olaparib treatment. Interestingly, both OlapR cell lines harbor increased DNA damage relative to parental cells, suggesting that OlapR cells accumulate and manage persistent DNA damage during acquisition of resistance, likely through augmenting DNA repair capacity. Further impairing DNA repair through CDK1 inhibition enhances DNA damage, induces cell death, and sensitizes OlapR cells to olaparib treatment. Our data together further our understanding of PARPi treatment and provide a cellular platform system for the study of response and resistance to PARP inhibition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.